Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity
Author(s)
Type
Journal Article
Abstract
The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-deficient mice are incapable of forming germinal centers or generating plasma B cells upon either viral infection or immunization. Such severe immune deficiency is caused by multiple and profound B cell abnormalities, including early blocks during B cell development; impaired antigen-driven BCR signaling and actin remodeling; defective antigen presentation and in vivo interaction with T cells; and a severe B cell-intrinsic block in plasma cell differentiation. Thus, our study presents a new perspective on Cdc42 as key regulator of B cell physiology.
Date Issued
2015-01
Date Acceptance
2014-11-25
Citation
Journal of Experimental Medicine, 2015, 212 (1), pp.53-72
ISSN
0022-1007
Publisher
Rockefeller University Press
Start Page
53
End Page
72
Journal / Book Title
Journal of Experimental Medicine
Volume
212
Issue
1
Copyright Statement
© 2015 Burbage et al. This article is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/25547673
PII: jem.20141143
Subjects
Animals
Antibody Formation
B-Lymphocytes
Bone Marrow Cells
Cell Differentiation
Cells, Cultured
Flow Cytometry
Gene Expression
Germinal Center
Immunity, Humoral
Influenza A virus
Lymphoid Tissue
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Confocal
Microscopy, Electron
Orthomyxoviridae Infections
Reverse Transcriptase Polymerase Chain Reaction
cdc42 GTP-Binding Protein
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2014-12-29